Practical, Asymmetric Route to Sitagliptin and Derivatives: Development and Origin of Diastereoselectivity
The development of a practical and scalable process for the asymmetric synthesis of sitagliptin is reported. Density functional theory calculations reveal that two noncovalent interactions are responsible for the high diastereoselection. The first is an intramolecular hydrogen bond between the enami...
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Veröffentlicht in: | Organic letters 2015-04, Vol.17 (7), p.1742-1745 |
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Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | The development of a practical and scalable process for the asymmetric synthesis of sitagliptin is reported. Density functional theory calculations reveal that two noncovalent interactions are responsible for the high diastereoselection. The first is an intramolecular hydrogen bond between the enamide NH and the boryl mesylate SO, consistent with MsOH being crucial for high selectivity. The second is a novel C–H···F interaction between the aryl C5-fluoride and the methyl of the mesylate ligand. |
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ISSN: | 1523-7060 1523-7052 |
DOI: | 10.1021/acs.orglett.5b00520 |